title: Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy.
abstract: Although there is tremendous interest in stem cell (SC)-based therapies for cardiomyopathy caused by chronic myocardial infarction, many unanswered questions regarding the best approach remain. The TAC-HFT study is a phase I/II randomized, double-blind, placebo-controlled trial designed to address several of these questions, including the optimal cell type, delivery technique, and population. This trial compares autologous mesenchymal SCs (MSCs) and whole bone marrow mononuclear cells (BMCs). In addition, the study will use a novel helical catheter to deliver cells transendocardially. Although most trials have used intracoronary delivery, the optimal method is unknown and data suggest that the transendocardial approach may have important advantages. Several trials support the benefit of SCs in patients with chronic ischemic cardiomyopathy (ICMP), although the sample sizes have been small and the number of trials sparse. After a pilot phase of 8 patients, 60 patients with ICMP (left ventricular ejection fraction 15%-50%) will be randomized to group A (30 patients further randomized to receive MSC injection or placebo in a 2:1 fashion) or group B (30 patients further randomized to BMCs or placebo in a 2:1 fashion). All patients will undergo bone marrow aspiration and transendocardial injection of SCs or placebo. The primary and secondary objectives are, respectively, to demonstrate the safety and efficacy (determined primarily by cardiac magnetic resonance imaging) of BMCs and MSCs administered transendocardially in patients with ICMP.
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Leonard Miller School of Medicine, FL, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Trachtenberg
authors.forename: Darcy L
authors.initials: DL
authors.lastname: Velazquez
authors.forename: Adam R
authors.initials: AR
authors.lastname: Williams
authors.forename: Ian
authors.initials: I
authors.lastname: McNiece
authors.forename: Joel
authors.initials: J
authors.lastname: Fishman
authors.forename: Kim
authors.initials: K
authors.lastname: Nguyen
authors.forename: Didier
authors.initials: D
authors.lastname: Rouy
authors.forename: Peter
authors.initials: P
authors.lastname: Altman
authors.forename: Richard
authors.initials: R
authors.lastname: Schwarz
authors.forename: Adam
authors.initials: A
authors.lastname: Mendizabal
authors.forename: Behzad
authors.initials: B
authors.lastname: Oskouei
authors.forename: John
authors.initials: J
authors.lastname: Byrnes
authors.forename: Victor
authors.initials: V
authors.lastname: Soto
authors.forename: Melissa
authors.initials: M
authors.lastname: Tracy
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Zambrano
authors.forename: Alan W
authors.initials: AW
authors.lastname: Heldman
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D016026:Bone Marrow Transplantation / Q000379:methods*; D004311:Double-Blind Method; D006333:Heart Failure / Q000209:etiology / Q000628:therapy*; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009203:Myocardial Infarction / Q000150:complications; D020858:Tissue and Organ Harvesting; D014182:Transplantation, Autologous; D018487:Ventricular Dysfunction, Left / Q000628:therapy*